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1.
Sci Rep ; 14(1): 23667, 2024 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390078

RESUMO

Previous research has suggested that circulating inflammatory proteins are associated with benign prostatic disease (BPD). This Mendelian randomization (MR) study was conducted to further investigate the causal relationship between 91 inflammatory proteins and BPD. Genome-wide association study (GWAS) summarized data of benign prostatic hyperplasia (BPH) and prostatitis were obtained from the FinnGen Biobank. The latest study offered the GWAS data on 91 proteins related to inflammation. We performed a bidirectional MR to investigate the causal association between inflammatory proteins and BPD. The outcomes of the IVW method indicated that decreased levels of circulating interleukin-17 C (IL-17 C) (OR = 0.92, 95%CI = 0.85-0.99, p-value = 0.0344) were suggestively associated with a higher risk of BPH and elevated levels of interleukin-10 receptor subunit alpha (IL-10RA) (OR = 1.24, 95%CI = 1.05-1.47, p-value = 0.0132) and urokinase-type plasminogen activator (uPA) (OR = 1.13, 95%CI = 1.00-1.28, p-value = 0.0421) were suggestively related to a higher risk of prostatitis. Furthermore, reverse MR revealed that BPH may promote the expression of circulating factors, including natural killer cell receptor 2B4 (CD244) (OR = 1.07, 95%CI = 1.01-1.13, p-value = 0.0192), T-cell surface glycoprotein CD6 isoform (CD6) (OR = 1.07, 95%CI = 1.01-1.13, p-value = 0.0192), and leukemia inhibitory factor receptor (LIF-R) (OR = 1.07, 95%CI = 1.01-1.15, p-value = 0.0163). Moreover, the results of sensitivity analyses indicate that heterogeneity and horizontal pleiotropy are unlikely to distort the findings. The results of this study indicate a potential association between circulating inflammatory proteins and BPD, which may become new diagnostic indicators or drug targets for clinical application in the prevention and treatment of BPD. However, further investigation is required.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Prostatite/sangue , Prostatite/genética , Inflamação/sangue , Inflamação/genética , Biomarcadores/sangue
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(9): 1384-1387, 2024 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-39290021

RESUMO

To study the clinical correlation between fasting plasma glucose, lipid metabolism, prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia, and to explore the combined effect as diagnostic indicators. A total of 108 patients with benign prostatic hyperplasia treated in Beijing University of Chinese Medicine Third Affiliated Hospital from June 2021 to March 2023 were retrospectively analyzed as the hyperplasia group, and 98 healthy physical examination personnel were selected as the control group during the same period. Compare the differences in levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small and dense low-density lipoprotein cholesterol (sdLDL-C), homocysteine, lipoprotein a (LPa), prostate specific antigen (PSA), and free prostate specific antigen (fPSA) between two groups of patients. Using Pearson analysis method to analyze the correlation between the above indicators and the size of prostate volume in patients with benign prostatic hyperplasia; using multiple linear regression to analyze the influencing factors of prostate volume enlargement; draw receiver operating characteristic (ROC) curves and analyze the application value of individual and combined detection of HDL, FPG, PSA, and fPSA. The results showed that there were significant differences in HDL, FPG, PSA, and fPSA levels between the control group and the proliferative group(P<0.05). The size of prostate volume is negatively correlated with HDL(r=-0.183, P<0.05) and positively correlated with FPG (r=0.202, P<0.05), PSA(r=0.412, P<0.05), and fPSA(r=0.425, P<0.05). The results of multiple linear regression analysis showed that HDL(P=0.000), FPG(P=0.048), PSA(P=0.044), and fPSA (P=0.012) were risk factors for increased volume of benign prostatic hyperplasia; ROC curve analysis shows that the AUC of HDL, FPG, PSA, and fPSA combined detection is 0.823, which is better than individual detection. In conclusion,HDL, FPG, PSA, fPSA has close correlation with hyperplasia of prostate, the joint detection may has better prediction for benign prostatic hyperplasia.


Assuntos
Glicolipídeos , Antígeno Prostático Específico , Próstata , Hiperplasia Prostática , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Humanos , Masculino , Estudos Retrospectivos , Antígeno Prostático Específico/sangue , Próstata/patologia , Glicemia , Triglicerídeos/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Casos e Controles
3.
Cells ; 13(15)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39120316

RESUMO

BACKGROUND: Prostate cancer is the second most common cancer in males worldwide, and its incidence is rising. Early detection is crucial for improving the outcomes, but the current screening methods have limitations. While prostate-specific antigen (PSA) testing is the most widely used screening tool, it has poor specificity, leading to a high rate of false positives and unnecessary biopsies. The existing biopsy techniques are invasive and are associated with complications. The liquid biopsy methods that analyze the biomarkers in blood or other bodily fluids offer a non-invasive and more accurate alternative for detecting and characterizing prostate tumors. METHODS: Here, we present a novel liquid biopsy method for prostate cancer based on the identification of specific proteins in the extracellular vesicles isolated from the blood of patients with prostate cancer. RESULTS: We observed that a specific combination of sEV proteins is a sensitive indicator of prostate cancer. Indeed, we found that the number of clusters expressed by specific combinations of either intra-vesicular (STAT3 and CyclinD1) or surface proteins (ERBB3, ALK, and CD81) allowed us to significantly discriminate the patients with prostate cancer from the individuals with hyperplasia. CONCLUSION: This new liquid biopsy method has the potential to improve prostate cancer screening by providing a non-invasive and more accurate diagnostic tool.


Assuntos
Biomarcadores Tumorais , Vesículas Extracelulares , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Biópsia Líquida/métodos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Vesículas Extracelulares/metabolismo , Diagnóstico Diferencial , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Idoso , Pessoa de Meia-Idade
4.
Aging Male ; 27(1): 2388529, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39135319

RESUMO

OBJECTIVE: Prostate hyperplasia and cancer are more prevalent in middle-aged and elderly men. Previous studies have linked both disorders to androgen receptors. Herein, efforts were made to identify factors associated with prostate cancer in patients ≥60 years, aiming to enhance their health management. METHODS: An analytical framework was established utilizing the "Prostate Cancer Early Warning Dataset" from the National Clinical Medical Science Data Center. Variables selection was conducted through LASSO regression, followed by multifactorial logistic stepwise regression to construct a predictive model. RESULTS: A total of 1,502 patients with BPH and 294 with combined PCa were hereby included. Multivariate regression delineated several independent predictors of PCa coexistence, including age (OR [95% CI]: 1.06 [1.04-1.09], p < 0.001), fPSA/tPSA ratio (OR [95% CI]: 0.01 [0.002-0.05], p < 0.001), serum inorganic phosphorus (OR [95% CI]: 5.85 [2.61-13.15], p < 0.001), globulin levels (OR [95% CI]: 1.06 [1.02-1.11], p = 0.005), serum potassium (OR [95% CI]: 0.58 [0.40-0.86], p = 0.006), low-density lipoprotein (LDL) cholesterol (OR [95% CI]: 1.28 [1.06-1.54], p = 0.009), among others. CONCLUSION: The analysis revealed connections between PCa occurrence in men aged over 60 and BPH, along with specific serum biomarkers such as inorganic phosphorus, globulin, LDL cholesterol, lower fPSA/tPSA ratios and serum potassium.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Antígeno Prostático Específico/sangue , Fatores Etários , Idoso de 80 Anos ou mais , Modelos Logísticos
5.
Int J Urol ; 31(10): 1087-1094, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39007219

RESUMO

OBJECTIVES: This study aims to evaluate the impact of anterior fibromuscular stroma preserved enucleation (AFSPE) of the prostate on serum testosterone levels in patients with benign prostatic obstruction (BPO) and to explore age-related differences in postoperative testosterone elevation. METHODS: In a retrospective analysis, 304 patients from a pool of 560 who underwent AFSPE at Linkou Chang Gung Memorial Hospital between January 2018 and December 2021 were evaluated. Patients were stratified based on preoperative testosterone levels into low (<3.5 ng/mL) and normal (≥3.5 ng/mL) groups. Serum testosterone levels were measured preoperatively, at 1.5 and 3-6 months postoperatively. Age and other demographic data were analyzed as potential factors influencing testosterone changes. RESULTS: The low-testosterone group (n = 90) showed significant testosterone increases, from an average of 2.61 ng/mL preoperatively to 3.3 ng/mL at 1.5 months and 3.59 ng/mL at 3-6 months postoperatively (p < 0.0001). The normal-testosterone group (n = 214) maintained stable testosterone levels at 1.5 months but exhibited a significant rise to 6.06 ng/mL by 3-6 months (p = 0.0079). Older age was inversely associated with postoperative testosterone elevation in both groups. Improvements in nocturia were notable in both groups. CONCLUSIONS: AFSPE of the prostate significantly elevates serum testosterone levels in men with BPO, particularly benefiting those initially with low levels. Age is a crucial factor influencing postoperative testosterone changes, indicating that younger patients may benefit more from this intervention. AFSPE offers a promising approach for improving hormonal health in BPO patients, alongside alleviating urinary symptoms.


Assuntos
Hiperplasia Prostática , Testosterona , Humanos , Masculino , Testosterona/sangue , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/sangue , Fatores Etários , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Próstata/cirurgia , Próstata/patologia , Período Pós-Operatório , Idoso de 80 Anos ou mais
6.
Front Biosci (Landmark Ed) ; 29(7): 256, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39082359

RESUMO

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors of the male urinary system, and its incidence and mortality rates have been increasing worldwide. Benign prostatic hyperplasia (BPH) represents stromal and epithelial cell proliferation in the prostate in elderly males. Abnormal activation of inflammation-related signalling molecules, such as toll-like receptor 4 (TLR4) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) has been linked to the initiation and progression of various human diseases including PCa and BPH. Cylindromatosis (CYLD) gene alterations are associated with PCa progression. In this study, the contribution of CYLD, JAK2, and TLR4 gene variants to PCa and BPH risks and their associations with prostate-specific antigen (PSA) levels, immunophenotype, and clinical features in Vietnamese men were determined. METHODS: A total of 102 patients with PCa, 65 with BPH, and 114 healthy controls were enrolled. The immunophenotype was analyzed by flow cytometry, cytokine secretion by enzyme-linked immunosorbent assay (ELISA), and gene variants by DNA sequencing. RESULTS: Lower levels of transforming growth factor ß (TGF-ß) and higher numbers of CD13+CD117- and CD56+CD25+ cells were observed in the PCa group than in the BPH group. Genetic analysis of the CYLD gene identified five single nucleotide polymorphisms (SNPs), of which c.2351-47 C>T, c.2351-46A>T, and rs1971432171 T>G had significantly higher frequencies in PCa patients than in the control and BPH groups. Sequencing of the TLR4 gene revealed five nucleotide changes, in which the rs2149356 SNP showed an increased risk for both PCa and BPH and the c.331-206 SNP had a reduced risk for PCa. Importantly, the expansion of activated natural killer (NK) cells and higher levels of PSA were found in PCa patients carrying the CT genotype of the CYLD c.2351-47 compared to those with the wild-type genotype. CONCLUSION: Activation of NK cells in CYLD-sensitive PCa patients was associated with serum PSA release and the CYLD c.2351-47 variant may be a significant risk factor for prostatitis in PCa patients.


Assuntos
Enzima Desubiquitinante CYLD , Janus Quinase 2 , Antígeno Prostático Específico , Hiperplasia Prostática , Neoplasias da Próstata , Receptor 4 Toll-Like , Humanos , Masculino , Hiperplasia Prostática/genética , Hiperplasia Prostática/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/sangue , Receptor 4 Toll-Like/genética , Enzima Desubiquitinante CYLD/genética , Enzima Desubiquitinante CYLD/metabolismo , Antígeno Prostático Específico/sangue , Idoso , Janus Quinase 2/genética , Pessoa de Meia-Idade , Imunofenotipagem , Genótipo , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles
7.
PLoS One ; 19(7): e0306860, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38980876

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common health disorder of the male genitourinary system with a high prevalence, especially among middle-aged and older adults, which seriously affects men's quality of life. Inflammatory markers derived from complete blood cell count (CBC) have previously been considered a prognostic indicator for various diseases, but little is known about their relationship with BPH. This study evaluated the relationship between complete blood cell count (CBC)-derived inflammatory biomarkers and BPH. METHODS: Data for this cross-sectional study were gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2008. Using multiple logistic regressions, the study examined the association between benign prostatic hyperplasia(BPH) and Inflammatory biomarkers derived from blood cell counts such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), Systemic Inflammatory Response Index (SIRI) and Systemic Immunoinflammatory Index (SII). RESULTS: 3,919 participants were included, with a median age of 61.00 (52.00-71.00) years old. Among them, 609 participants had benign prostatic hyperplasia, with a prevalence of 15.54%. Upon accounting for confounding factors, the study revealed a positive correlation between the plurality of BPH PLR and SII. However, MLR, NLR, and SIRI did not significantly correlate with the prevalence of BPH (p>0.05). In contrast to the lowest quartile, higher quartiles of PLR (OR = 1.93[1.38-2.69]) and SII (OR = 1.71[1.22-2.40]) were linked to an elevated risk of BPH. Interaction tests showed that age, body mass index, hypertension, diabetes, smoking, and drinking had no significant effect on this positive correlation (p for interaction>0.05). In addition, we found a roughly linear association between SII, PLR, and BPH using smoothed curve fitting. CONCLUSIONS: According to our research, high levels of PLR and SII are positively linked with an increased risk of BPH in middle-aged and elderly individuals in the United States. The results compensate for previous studies that still need to be validated with larger prospective cohorts.


Assuntos
Biomarcadores , Inquéritos Nutricionais , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Pessoa de Meia-Idade , Idoso , Biomarcadores/sangue , Estados Unidos/epidemiologia , Estudos Transversais , Contagem de Células Sanguíneas , Inflamação/sangue , Monócitos/metabolismo , Linfócitos , Neutrófilos , Prevalência
8.
Biosens Bioelectron ; 263: 116603, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39067414

RESUMO

Biosensors based on carbon nanotube field-effect transistors (CNT-FETs) have shown great potential in biomarker detection due to their high sensitivity because of appreciable semiconducting electrical properties. However, background signal interferences in complex mediums may results in low signal-to-noise ratio, which may impose challenges for precise biomarker detection in physiological fluids. In this work, we develop an enzymatic CNT-FET, with scalable production at wafer scale, for detection of trace sarcosine that is a biopsy-correlated biomarker of prostate cancer. Enzymatic cascade rectors are constructed on the CNT to improve the reaction efficiency, thereby, enhancing the signal transduction. As such, a limit of detection as low as 105 zM is achieved in buffer solution. Owing to the enhanced reaction efficiency, the testing of clinical serum samples yields significant signal difference to discriminate the prostate cancer (PCa) samples from the benign prostatic hyperplasia (BPH) samples (P = 1.07 × 10-5), demonstrating immense potential in practical applications.


Assuntos
Biomarcadores Tumorais , Técnicas Biossensoriais , Nanotubos de Carbono , Neoplasias da Próstata , Transistores Eletrônicos , Nanotubos de Carbono/química , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/sangue , Técnicas Biossensoriais/instrumentação , Biomarcadores Tumorais/sangue , Limite de Detecção , Sarcosina/sangue , Sarcosina/análise , Desenho de Equipamento , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/sangue
9.
Prostate ; 84(12): 1128-1137, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38824441

RESUMO

BACKGROUND: The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development. METHODS: In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis. RESULTS: Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue. CONCLUSIONS: The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , Antígeno Prostático Específico , Hiperplasia Prostática , Neoplasias da Próstata , Sêmen , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Idoso , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Hiperplasia Prostática/genética , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Sêmen/metabolismo , Sêmen/química , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/genética , Ácidos Nucleicos Livres/sangue , Galectina 3/genética , Galectina 3/metabolismo , Galectina 3/sangue , Sensibilidade e Especificidade , Proteínas Sanguíneas , Galectinas
10.
Cancer Immunol Immunother ; 73(8): 139, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833027

RESUMO

BACKGROUND: The significance of tumor-secreted cytokines in tumor development has gained substantial attention. Nevertheless, the precise role of tumor-related inflammatory cytokines in prostate cancer (PCa) remains ambiguous. OBJECTIVES: To gain deeper insights into the inflammatory response in the process of PCa. METHODS: A total of 233 cases were collected, including 80 cases of prostate hyperplasia as disease control, 65 cases of postoperative prostate cancer and 36 cases of prostate cancer as PCa group. Additionally, 52 patients undergoing physical examinations during the same period were collected as the healthy control. The levels of 12 inflammatory cytokines in peripheral blood samples were analyzed using flow cytometric bead array technology. The levels of total prostate-specific antigen (TPSA) and free prostate-specific antigen (FPSA) in peripheral blood samples were analyzed using electrochemiluminescence technology. RESULTS: Our findings revealed significant increases in serum IL-8 levels in PCa group compared to the healthy control group. Additionally, IL-6, IL-10, IFN-γ and IL-12p70 levels were markedly elevated in the PCa group compared to the disease control group (all p < 0.05). Conversely, the level of IL-4, TNF-α, IL-1ß, IL-17A and IFN-α were lower in the PCa group compared to those in control group. Following surgery, the concentration of IL-6 decreased; whereas, the concentrations of IL-4, TNF-α, IL-17A, IL-1ß, IL-12p70, and IFN-α increased, demonstrating significant differences (p < 0.05). The differential upregulation of IL-6 or downregulation of IL-17A in peripheral blood exhibited diagnostic efficacy in PCa patients. Moreover, we observed a significant increase in IL-17A levels, accompanied by decreased of IL-2, IL-4, IL-10, TNF-a, IFN-γ, IL-1ß, and IL-12P70 in patients with distant metastasis. CONCLUSION: The peripheral blood cytokines are closely associated with the occurrence and development of prostate cancer, especially the serum levels of IL-6 and IL-17A may be useful as potential predictors of PCa diagnosis.


Assuntos
Citocinas , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/sangue , Citocinas/sangue , Citocinas/metabolismo , Pessoa de Meia-Idade , Idoso , Diagnóstico Diferencial , Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/sangue
11.
J Pharm Biomed Anal ; 248: 116264, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38889577

RESUMO

Anemarrhena asphodeloides Bunge-Phellodendron chinense Schneid (AAPC) is one of the most widely accepted herb pairs in Chinese medicine prescription for treating benign prostatic hyperplasia (BPH). However, the mechanisms underlying the combination of the two herbs for anti-BPH are still not completely clear. To uncover the potential mechanism of the AAPC herb pair in the treatment of BPH, chemical profiling, network pharmacology, serum metabonomics and experimental validation were integrated. UHPLC-Q-Exactive Orbitrap-MS was performed to characterize the chemical profiling of the herb pair extract, and network pharmacology was employed to forecast the potential effective components, core targets and key signaling pathways. Then, western blot and RT-PCR experiments were conducted to verify the PI3K/Akt/NF-κB signaling pathway predicted by network pharmacology. Finally, the serum differential metabolites and metabolic pathways were analyzed by serum non-targeted metabonomics, and these results were jointly analyzed by MetScape. 51 chemical components of the AAPC herb pair extract were identified, including phellodendrine, magnoflorine, berberine, mangiferin, anemarsaponin BIII, etc. In network pharmacology, the predicted core targets of these components include AKT1, TNF, EGFR, PTGS2, PIK3CA, etc. The KEGG pathway enrichment analysis indicated that PI3K-Akt, Rap1 and MAPK signaling pathways may play a key role in the AAPC herb pair for the treatment of BPH, and the results of animal experiments demonstrated that the herb pair could significantly inhibit the activation and expression of p-PI3K/PI3K, p-Akt/Akt, p-NF-κB/NF-κB in protein and mRNA levels. Furthermore, 31 serum differential metabolites and three main metabolic pathways were obtained by serum non-targeted metabonomics. And the crucial metabolic pathway of arachidonic acid (AA) was obtained by integrated analysis of network pharmacology and metabonomics results. In conclusion, the AAPC herb pair can improve BPH through inhibiting the activation and expression of the PI3K/Akt/NF-κB signaling pathway and AA metabolism.


Assuntos
Anemarrhena , Medicamentos de Ervas Chinesas , Metabolômica , Farmacologia em Rede , Phellodendron , Hiperplasia Prostática , Transdução de Sinais , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/sangue , Masculino , Anemarrhena/química , Metabolômica/métodos , Farmacologia em Rede/métodos , Phellodendron/química , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Transdução de Sinais/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia
12.
Sci Rep ; 14(1): 14765, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926454

RESUMO

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.


Assuntos
Hiperplasia Prostática , Neoplasias da Próstata , Células-Tronco , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/sangue , Células-Tronco/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Próstata/patologia , Próstata/metabolismo , Diferenciação Celular , Proliferação de Células , Citocinas/metabolismo , Citocinas/sangue , Células Cultivadas , Idoso , Pessoa de Meia-Idade
13.
J Integr Neurosci ; 23(6): 123, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38940081

RESUMO

OBJECTIVE: Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. METHODS: A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. RESULTS: Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. CONCLUSION: The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. CLINICAL TRIAL REGISTRATION: Registered (ChiCTR2000028836). Date (20190306).


Assuntos
Ressecção Transuretral da Próstata , Humanos , Masculino , Idoso , Ressecção Transuretral da Próstata/efeitos adversos , Proteômica , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/sangue , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/sangue , Transtornos Neurocognitivos/metabolismo , Complicações Cognitivas Pós-Operatórias/etiologia , Complicações Cognitivas Pós-Operatórias/sangue , Período Perioperatório , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Biologia Computacional
14.
Int Braz J Urol ; 50(5): 572-584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38787616

RESUMO

OBJECTIVE: With the development of analytical methods, mathematical models based on humoral biomarkers have become more widely used in the medical field. This study aims to investigate the risk factors associated with the occurrence of bladder spasm after transurethral resection of the prostate (TURP) in patients with prostate enlargement, and then construct a nomogram model. MATERIALS AND METHODS: Two hundred and forty-two patients with prostate enlargement who underwent TURP were included. Patients were divided into Spasm group (n=65) and non-spasm group (n=177) according to whether they had bladder spasm after surgery. Serum prostacyclin (PGI2) and 5-hydroxytryptamine (5-HT) levels were measured by enzyme-linked immunoassay. Univariate and multivariate logistic regression were used to analyze the risk factors. RESULTS: Postoperative serum PGI2 and 5-HT levels were higher in patients in the Spasm group compared with the Non-spasm group (P<0.05). Preoperative anxiety, drainage tube obstruction, and elevated postoperative levels of PGI2 and 5-HT were independent risk factors for bladder spasm after TURP (P<0.05). The C-index of the model was 0.978 (0.959-0.997), with a χ2 = 4.438 (p = 0.816) for Hosmer-Lemeshow goodness-of-fit test. The ROC curve to assess the discrimination of the nomogram model showed an AUC of 0.978 (0.959-0.997). CONCLUSION: Preoperative anxiety, drainage tube obstruction, and elevated postoperative serum PGI2 and 5-HT levels are independent risk factors for bladder spasm after TURP. The nomogram model based on the aforementioned independent risk factors had good discrimination and predictive abilities, which may provide a high guidance value for predicting the occurrence of bladder spasm in clinical practice.


Assuntos
Nomogramas , Hiperplasia Prostática , Serotonina , Ressecção Transuretral da Próstata , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/sangue , Idoso , Ressecção Transuretral da Próstata/efeitos adversos , Fatores de Risco , Serotonina/sangue , Pessoa de Meia-Idade , Biomarcadores/sangue , Espasmo/etiologia , Espasmo/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Curva ROC , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/sangue , Valores de Referência
15.
Genes (Basel) ; 15(5)2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38790213

RESUMO

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais , MicroRNAs , Hiperplasia Prostática , Neoplasias da Próstata , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Idoso , Pessoa de Meia-Idade , Hiperplasia Prostática/genética , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Projetos Piloto , Regulação Neoplásica da Expressão Gênica
16.
Fr J Urol ; 34(6): 102643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38759841

RESUMO

AIM: This study aimed to investigate the clinical significance of neutrophil-to-lymphocyte ratio and ultrasonic parameters in diagnosing bladder outlet obstruction in patients with benign prostatic hyperplasia. MATERIAL: Between September 2022 and January 2024, a total of 106 patients with benign prostatic hyperplasia were collected from Hongqi Hospital affiliated to Mudanjiang Medical University followed by urodynamic testing. The patients were categorized into three groups based on the International Prostate Symptom Score: mild (45 cases), moderate (36 cases), and severe (25 cases). Thirty-five healthy men were recruited at the hospital as a control group. All patients had blood tests and ultrasound scans. RESULTS: Neutrophil-to-lymphocyte ratio, detrusor wall thickness, detrusor muscle elastic modulus, internal gland elastic modulus, intravesical prostatic protrusion, and post-voiding residual volume were significantly correlated with the bladder outlet obstruction stage and showed good diagnostic efficiency (all P<0.05. There was no statistically significant difference observed in the external gland elastic modulus between the experimental group and the control group (P>0.05). CONCLUSIONS: The neutrophil-to-lymphocyte ratio, detrusor wall thickness, elastic modulus of the detrusor and glandular gland may hold clinical significance for diagnosing bladder outlet obstruction resulting from benign prostatic hyperplasia.


Assuntos
Linfócitos , Neutrófilos , Hiperplasia Prostática , Ultrassonografia , Obstrução do Colo da Bexiga Urinária , Humanos , Masculino , Obstrução do Colo da Bexiga Urinária/diagnóstico por imagem , Obstrução do Colo da Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/etiologia , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/patologia , Hiperplasia Prostática/sangue , Hiperplasia Prostática/complicações , Neutrófilos/patologia , Ultrassonografia/métodos , Pessoa de Meia-Idade , Idoso , Linfócitos/patologia , Contagem de Leucócitos , Estudos de Casos e Controles , Contagem de Linfócitos
17.
Aging Male ; 27(1): 2336625, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38647199

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) affects 30% of men worldwide, folate is essential for life. However, few studies have investigated the relationship between folate levels and BPH. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator of long-term folate intake, and BPH in United States (US) men. METHODS: We used statistics from four cycles of the "National Health and Nutrition Examination Survey" (NHANES2001-2008), RBC folate data come from laboratory data and BPH date come from questionnaire data. A multivariate conditional logistic regression model and subgroup analysis were using to assess the association between RBC folate and BPH. RESULTS: 647 males from four survey cycles in the NHANES2001-2008, of which, 574 men (88.7%) had BPH. After adjusting for potential confounders, a considerable correlation was observed between RBC folate and BPH; With the first quintiles of RBC folate as the reference, multivariable-adjusted odds ratios (ORs) and confidence intervals (95% CIs) of the second, third, fourth, and the highest quintiles were 1.19 (0.58 ∼ 2.44), 1.39 (0.65 ∼ 2.97), 2.27 (0.96 ∼ 5.39), 2.26 (1.35 ∼ 3.76) and 5.37 (1.85 ∼ 15.59), respectively. CONCLUSIONS: Individuals with high levels of RBC folate were associated with an increased risk of self-reported benign prostatic hyperplasia of US men.


Assuntos
Eritrócitos , Ácido Fólico , Inquéritos Nutricionais , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/sangue , Hiperplasia Prostática/epidemiologia , Ácido Fólico/sangue , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Eritrócitos/química , Eritrócitos/metabolismo , Idoso , Adulto , Modelos Logísticos , Fatores de Risco
18.
Anal Sci ; 40(6): 1101-1110, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38468109

RESUMO

Discovering the balance between toxicity and efficacy for many drugs requires therapeutic drug monitoring (TDM) of their concentrations in the blood. Here, a hot-embossed microfluidic device with a new design integrated to a nanofracture is presented for purification of blood samples from numerous proteins and cells, allowing to the separation of small molecules from blood matrix. The device was used to separate and quantitatively detect tamsulosin drug after derivatization with fluorescamine reagent, allowing converting it from a neutral molecule into a charged fluorescent complex under the experimental conditions, and thus its separation by electrophoresis. The device is portable and easy operated, and the presented method showed good linearity (R2 = 0.9948) over a concentration range of 0.1-1 µg/mL. The relative standard deviation (RSD%) was below 10% (n = 3), indicating good precisions, and the limit of detection (LOD) and limit of quantitation (LOQ) values were estimated to be 0.1 and 0.55 µg/mL, respectively. Whole blood samples from 10 patients with benign prostatic hyperplasia (BPH) were analyzed, showing good percentage recoveries of tamsulosin in whole blood. This point-of-care (POC), low-cost method could increase the convenience of patients and doctors, make therapies safer, and make TDM available in different regions and places.


Assuntos
Monitoramento de Medicamentos , Sistemas Automatizados de Assistência Junto ao Leito , Hiperplasia Prostática , Tansulosina , Tansulosina/sangue , Humanos , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Masculino , Nanotecnologia , Dispositivos Lab-On-A-Chip
19.
Biochem Pharmacol ; 197: 114889, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979091

RESUMO

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men.


Assuntos
Compostos Benzidrílicos/toxicidade , Estrogênios não Esteroides/toxicidade , Fenóis/toxicidade , Hiperplasia Prostática/induzido quimicamente , Doenças Urológicas/induzido quimicamente , Animais , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/química , Estrogênios não Esteroides/sangue , Estrogênios não Esteroides/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenóis/sangue , Fenóis/química , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Doenças Urológicas/sangue , Doenças Urológicas/patologia
20.
Urology ; 159: 16-21, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626600

RESUMO

OBJECTIVE: To investigate the effect of SARS CoV-2 on serum total PSA levels in men with BPH diagnosed with COVID-19. METHODS: The PSA (Kit: Immunoassay Program- Cycle 18, Siemens Atellica IM Analyzer) levels in patients who had had a PSA check at least 3 months, but no more than 6 months, prior to diagnosis of acute COVID-19 infection, were examined retrospectively. PSA levels were measured and recorded from these patients on the first day of diagnosis of COVID-19. These patients were called back for urology outpatient follow-up at the third month after the end of the COVID-19 treatment. PSA levels measured in the pre-COVID-19 period, during the period of active infection with COVID-19, and in the post-COVID-19 period were compared. RESULTS: In total, 91 patients had a serum PSA level of 1.58 ± 1.09 ng/mL in the pre-COVID-19 period, a serum PSA level of 4.34 ± 3.78 ng/mL measured in the COVID-19 period and 2.09 ± 2.70 ng/mL in the post-COVID-19 period. It was determined that the serum PSA level measured during active COVID-19 infection was statistically significantly higher than the PSA levels measured according to the pre-COVID-19 period and the post-COVID-19 period (P < .001, P < .001; respectively). CONCLUSION: SARS-CoV-2 infection in men diagnosed with BPH causes significant increases in PSA levels during the active period of the disease. Measurement of PSA values used in the diagnosis, differential diagnosis, and follow-up of prostate diseases in the acute period of infection and in the early period after infection treatment may cause false evaluations that may affect the diagnosis and treatment steps of prostate diseases in these patients.


Assuntos
COVID-19/complicações , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/sangue
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